An Introduction to Systems Biology

Design Principles of Biological Circuits

Uri Alon

• Publisher: Chapman and Hall/CRC
• Year: 2019
• ISBN:
  9781000008166
• Edition: 2
• Topic: Mathematics
• Subtopic: Applied Mathematics
• Index: Mathematics

Praise for the first edition:

… superb, beautifully written and organized work that takes an engineering approach to systems biology. Alon provides nicely written appendices to explain the basic mathematical and biological concepts clearly and succinctly without interfering with the main text. He starts with a mathematical description of transcriptional activation and then describes some basic transcription-network motifs (patterns) that can be combined to form larger networks. – Nature

[This text deserves] serious attention from any quantitative scientist who hopes to learn about modern biology … It assumes no prior knowledge of or even interest in biology … One final aspect that must be mentioned is the wonderful set of exercises that accompany each chapter. … Alon's book should become a standard part of the training of graduate students. – Physics Today

Written for students and researchers, the second edition of this best-selling textbook continues to offer a clear presentation of design principles that govern the structure and behavior of biological systems. It highlights simple, recurring circuit elements that make up the regulation of cells and tissues. Rigorously classroom-tested, this edition includes new chapters on exciting advances made in the last decade.

Features:

• Includes seven new chapters
• The new edition has 189 exercises, the previous edition had 66
• Offers new examples relevant to human physiology and disease

The book website including course videos can be found here: https://www.weizmann.ac.il/mcb/UriAlon/introduction-systems-biology-design-principles-biological-circuits.

Part 1

Network Motifs

Chapter 1

Transcription Networks

Basic Concepts

1.1 Introduction

The cell is an integrated device made of several thousand types of proteins. Each protein is a nanometer-size molecular machine that carries out a specific task with exquisite precision. For example, the micron-long bacterium Escherichia coli is a cell that contains a few million proteins, of about 4500 different types (typical numbers, lengths and timescales can be found in Table 1.1).

Table 1.1 Typical Biological Parameter Values (Biology by the Numbers, 2016)
Property	E. coli	Yeast	Human (Fibroblast)
Cell volume	1 µm3	1000 µm3	10,000 µm3
Proteins/cell	∼4 × 106	∼4 × 109	∼4 × 1010
Mean size of protein	4–5 nm
Size of genome	4.6 × 106 bp 4500 genes	1.2 × 107 bp 6600 genes	3.2 × 109 bp 21,000 genes
Regulator binding site length	10–20 bp	5–10 bp	5–10 bp
Promoter length	∼100 bp	∼1000 bp	∼104–105 bp
Gene length	∼1000 bp	∼1000 bp	104–106 bp (with introns)
Concentration of 1 protein/cell	∼1 nM	∼1 pM	∼0.1 pM
Diffusion time of protein across cell	∼0.1 sec (D = 10 µm2/sec)	∼0.3 sec	∼10 sec
Diffusion time of small molecule across cell	∼1 msec (D = 100 µm2/sec)	∼3 msec	∼0.1 sec
Time to transcribe a gene	<1 min (80 bp/sec)	∼1 min	∼30 min (including RNA processing)
Time to translate a protein	<1 min (20 aa/sec)	∼1 min	∼30 min (including mRNA export)
Typical mRNA lifetime	3 min	30 min	10 h
Typical protein lifetime	1 h	0.3–3 h	10–100 h
Cell generation time	20 min-several hours	2h-several hours	20 h-nondividing
Ribosomes/cell	104	107	108
Mutation rate	10−9–10−10/bp/ replication	10−9–10−10/bp/ replication	∼10–9/bp/replication

Cells encounter different situations that require different proteins. For example, when cells sense sugar, they begin to produce proteins that transport the sugar into the cell and utilize it. When damaged, the cell produces repair proteins. The cell therefore continuously monitors its environment and calculates the amount at which each type of protein is needed. This information-processing function, which determines the rate of production of each protein, is largely carried out by transcription networks.

The first few chapters in this book will discuss transcription networks. This opening chapter defines the elements of transcription networks and their dynamics.

1.2 The Cognitive Problem of the Cell

Cells live in a complex environment and can sense many different signals, including physical parameters such as temperature and osmotic pressure, biological signaling molecules from other cells, beneficial nutrients and harmful chemicals. Information about the internal state of the cell, such as the level of key metabolites and internal damage (damage to DNA, membrane or proteins), is also important. Cells respond to these signals by producing appropriate proteins that act upon the internal or external environment.

To represent these environmental states, the cell uses special proteins called transcription factors as symbols. Transcription factors are designed to transit rapidly between active and inactive molecular states, at a rate that is modulated by ...